Sections

Medication

Medication Summary

The goals of therapy are to reduce morbidity, to shorten the clinical course of the disease, to prevent complications, and to prevent recurrences. Pharmacotherapy for herpes simplex encephalitis (HSE) is available in the form of acyclovir. Patient outcome is improved when this agent is used for treatment.

Class Summary

The goals of using antivirals are to shorten the clinical course, prevent complications, prevent development of latency and subsequent recurrences, decrease transmission, and eliminate established latency.

Acyclovir (Zovirax)

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Acyclovir is the drug of choice for HSE. It has demonstrated inhibitory activity against both herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) and is taken up selectively by infected cells. Mortality from HSE before use of acyclovir was 60-70%; since acyclovir, it is approximately 30%.

Famciclovir (Famvir)

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After ingestion, drug is rapidly biotransformed into the active compound penciclovir and phosphorylated by viral thymidine kinase. By competition with deoxyguanosine triphosphate, penciclovir triphosphate inhibits viral polymerase, subsequently inhibiting viral DNA synthesis/replication.

Adjust the dose in patients with renal insufficiency or hepatic disease.

Class Summary

Anticonvulsants are used to terminate clinical and electrical seizure activity as rapidly as possible and to prevent seizure recurrence.

Carbamazepine (Tegretol)

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Carbamazepine is effective in treatment of complex partial seizures; it appears to act by reducing polysynaptic responses and blocking posttetanic potentiation.

Phenytoin (Dilantin, Phenytek)

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Phenytoin is a hydantoin. Its primary site of action appears to be the motor cortex, where it may inhibit spread of seizure activity; it may reduce maximal activity of the brain stem centers responsible for the tonic phase of grand mal seizures.

The dose should be individualized; if daily dosage cannot be divided equally, larger dose should be given before bedtime. A phosphorylated formulation, fosphenytoin, is available for parenteral use.

Class Summary

These agents are used for the management of increased intracranial pressure in complications resulting from herpes simplex encephalitis.

Furosemide (Lasix)

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Furosemide is a loop diuretic that increases the excretion of water by interfering with the chloride-binding co-transport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. It increases renal blood flow without increasing the filtration rate. The onset of action generally is within 1 hour. It increases potassium, sodium, calcium, and magnesium excretion.

Furosemide is used in the acute setting for reduction of increased ICP. The proposed mechanisms in lowering ICP include following: (1) suppression of cerebral sodium uptake, (2) carbonic anhydrase inhibition resulting in decreased CSF production, and (3) inhibition of cellular membrane cation-chloride pump, thereby affecting the transport of water into astroglial cells.

The dose must be individualized to the patient. Depending on the response, administer at increments of 20-40 mg, no sooner than 6-8 hours after the previous dose, until desired diuresis occurs. When treating infants, titrate with 1-mg/kg/dose increments until a satisfactory effect is achieved.

Mannitol (Osmitrol)

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Mannitol reduces cerebral edema with the help of osmotic forces, and it decreases blood viscosity, resulting in reflex vasoconstriction and lowering of ICP.

Questions

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Media Gallery

Axial proton density-weighted image in 62-year-old woman with confusion and herpes encephalitis shows T2 hyperintensity involving right temporal lobe.
Axial gadolinium-enhanced T1-weighted image reveals enhancement of right anterior temporal lobe and parahippocampal gyrus. At right anterior temporal tip is hypointense, crescentic region surrounded by enhancement consistent with small epidural abscess.
Axial diffusion-weighted image reveals restricted diffusion in left medial temporal lobe consistent with herpes encephalitis. This patient also had positive result on polymerase chain reaction assay for herpes simplex virus, which is both sensitive and specific. In addition, patient had periodic lateralized epileptiform discharges on electroencephalography, which supports diagnosis of herpes encephalitis.

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Author

Shaheen E Lakhan, MD, PhD, MS, MEd, FAAN Clinical Professor of Neurology, Western University of Health Sciences

Shaheen E Lakhan, MD, PhD, MS, MEd, FAAN is a member of the following medical societies: American Academy of Neurology, American Medical Association, International Association for the Study of Pain

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cleveland Clinic; UCLA; MGH; California University of Science and Medicine; Carilion Clinic; Sage Therapeutics; The Learning Corp; Zogenix; Fern Health; Thriveworks; Click Therapeutics; Neurocrine; NeuroSport; SpineThera; Shaheen E. Lakhan, MD.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Aquestive, Bioserenity, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, Nexus, SK life science, Stratus, Sunovion, UCB<br/>Serve(d) as a speaker or a member of a speakers bureau for: Aquestive, Bioserenity, Ceribell, Eisai, Jazz, LivaNova, Neurelis, Neuropace, Nexus, SK life science, Stratus, Sunovion, UCB<br/>Received research grant from: Cerevel, LivaNova, Greenwich (Jazz), SK biopharmaceuticals, Takeda, Xenon.

Chief Editor

Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM Adjunct Associate Professor of Neurology, University of Missouri-Columbia School of Medicine; Medical Director of St Mary's Stroke Program, SSM Neurosciences Institute, SSM Health

Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Headache Society

Disclosure: Nothing to disclose.

Additional Contributors

Wayne E Anderson, DO, FAHS, FAAN Assistant Professor of Internal Medicine/Neurology, College of Osteopathic Medicine of the Pacific Western University of Health Sciences; Clinical Faculty in Family Medicine, Touro University College of Osteopathic Medicine; Clinical Instructor, Departments of Neurology and Pain Management, California Pacific Medical Center

Wayne E Anderson, DO, FAHS, FAAN is a member of the following medical societies: American Academy of Neurology, American Headache Society, California Medical Association, California Neurology Society, International Headache Society, San Francisco Medical Society, San Francisco Neurological Society

Disclosure: Nothing to disclose.

Ramon Diaz-Arrastia, MD, PhD Professor, Department of Neurology, University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School; Director, North Texas TBI Research Center, Comprehensive Epilepsy Center, Parkland Memorial Hospital

Ramon Diaz-Arrastia, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, New York Academy of Sciences, Phi Beta Kappa

Disclosure: Nothing to disclose.

Herpes Simplex Encephalitis Medication

Medication Summary

Antivirals

Class Summary

Acyclovir (Zovirax)

Acyclovir (Zovirax)

Famciclovir (Famvir)

Famciclovir (Famvir)

Anticonvulsants

Class Summary

Carbamazepine (Tegretol)

Carbamazepine (Tegretol)

Phenytoin (Dilantin, Phenytek)

Phenytoin (Dilantin, Phenytek)

Diuretics

Class Summary

Furosemide (Lasix)

Furosemide (Lasix)

Mannitol (Osmitrol)

Mannitol (Osmitrol)

Herpes Simplex Encephalitis Medication

Medication Summary

Antivirals

Class Summary

Acyclovir (Zovirax)

Acyclovir (Zovirax)

Famciclovir (Famvir)

Famciclovir (Famvir)

Anticonvulsants

Class Summary

Carbamazepine (Tegretol)

Carbamazepine (Tegretol)

Phenytoin (Dilantin, Phenytek)

Phenytoin (Dilantin, Phenytek)

Diuretics

Class Summary

Furosemide (Lasix)

Furosemide (Lasix)

Mannitol (Osmitrol)

Mannitol (Osmitrol)

References

Tables

Contributor Information and Disclosures

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